Anti-viral resistance in 2009 A/H1N1 flu - historical compilation of news

[Gert van der Hoek]

Re: Netherlands: Two die of Tamiflu resistant swine flu

Snip from weekly update RIVM (Dutch CDC) :

6 Tamiflu resistant patients - not related - 2 deaths - no wild virus, but Tamiflu induced - did not spread.

december 4, 2009

Until this week in the Netherlands diagnosed 6 patients, including 3 this week, with a pandemic A (H1N1) influenza virus which is resistant to the anti-viral drug Tamiflu (oseltamivir) that such patients are treated.

In all 6 cases no indication that it is naturally resistant viruses but that resistance has arisen due to the (long) treatment with Tamiflu.

The patients have a prolonged shedding of the influenza virus, in 5 of 6 patients probably due to an impaired immune defenses of these patients.

Two of the patients with underlying disease for which they were treated with chemotherapy are now deceased.

Around the 6 patients have so far no laboratory confirmed cases of transmission of resistant influenza virus found.

http://www.rivm.nl/cib/binaries/H1N1overzicht_tcm92-61018.pdf

[sharon sanders]

Tamiflu resistance in A/H1N1 flu - historical compilation of news

2009-12-04

Spain Introduces 2 November Sequences with Cross-Segment Pairing from Fatal Cases in the Ukraine

The HA and NA cross segment pairing of silent polymorphisms noted on the four fatal 225G cases from the Ukraine has now been tracked to 29 sequences around the globe on a cumulative study showing a quantifiable density in Spain.

• HA:syn413K encoded from A1281G, AAa->AAg *
• NA:syn407V encoded from T1221C, GTt->GTc *

* SNP Matches the 4 fatal flashfire cases

The most recent public database entries at GenBank are from Spain and were sampled in November 2009.

• HA and NA CatNS7362 TamiFlu Resistant
• HA and NA CatS1827

This background appears to be fertile ground and receptive to both major polymorphisms of interest today:

• HA 225G correlated with deep lung damage and one "low reactor" vaccine antisera challenge result
• NA 275Y conferring TamiFlu Resistance

The depth of this background continues to increase with 2 TamiFlu Resistant strains reported in 2 days. The persistance of this cross segment correlation may signal a viral genetic acquisition response to widespread TamiFlu usage. These silent polymorphisms are suggestive of an intermediate stage that is moving in the direction of antiviral resistance and continued Receptor Binding Domain revisions due to antiviral blanketing.

[Commonground]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

2 Drug-Resistant H1N1 Cases Reported In Pa.

Dec 4, 2009 8:21 pm US/Eastern

PITTSBURGH (KDKA) -The standard treatment for H1N1 is anti-flu drug Tamiflu, so when cases of Tamiflu-resistant H1N1 turn up, it is concerning.

There are two cases in our state. Public health officials and hospitals have a plan, if they're faced with a local case.

"Tamiflu has been our mainstay of therapy. And yes, as we get more and more resistance, we do have some concerns about that," says Dr. Bruce Dixon, of the Allegheny County Health Department.

The state lab has been testing whether the virus samples it receives would respond to this drug.

"They've detected two cases in the state, in the eastern part of the state, and I don't think that's unexpected. We're seeing growing numbers in the country of resistant viruses showing up, and we know flu mutates quite readily," Dr. Dixon continues.

A series of steps would be taken should there be a local patient with drug-resistant virus.

In the hospital, some aspects would be the same as if they were dealing with a regular strain.

"The isolation we would use for any influenza case would be the same, people wearing gloves, and surgical masks when they're seeing the patients, everybody would already be in a private room," explains Dr. Amesh Adalja, a critical care medicine fellow at UPMC.

The treatment, though, would be different with an alternate anti-flu drug -- Relenza. It is typically inhaled, but when a patient is very ill, it has to be given by vein and that requires special permission from the hospital and the drug company.

"There's no evidence that this virus causes any more damage than the regular one. The prognosis may be a little worse because it's harder to get effective antiviral treatment to this patient," says Dr Adalja.

The health department would also take action.

"We look carefully to see if there are other family members that are ill, if there are other friends in their immediate circle of acquaintances who have gotten infected," Dixon said. "We do that regularly with the severe cases of H1N1."

The health department is reminding people that they will be holding an H1N1 vaccine clinic again this weekend. The vaccine will help prevent Tamiflu resistant cases in general, by cutting down on the number of people with H1N1 all together.

[sharon sanders]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

Modeling gene sequences over time in 2009 H1N1 Influenza A Virus populations

Natalia Goni , Alvaro Fajardo , Gonzalo Moratorio , Rodney Colina and Juan Cristina
Virology Journal 2009, 6:215doi:10.1186/1743-422X-6-215
<table cellpadding="0" cellspacing="0"> <tbody> <tr> <td>
</td></tr><tr> <td>Published:</td> <td>4 December 2009</td> </tr> </tbody> </table>Abstract (provisional)

Background

A sudden emergence of Influenza A Virus (IAV) infections with a new pandemic H1N1 IAV is taking place since April of 2009. In order to gain insight into the mode of evolution of these new H1N1 strains, we performed a Bayesian coalescent Markov chain Monte Carlo (MCMC) analysis of full-length neuraminidase (NA) gene sequences of 62 H1N1 IAV strains (isolated from March 30th to by July 28th, 2009) . Results: The results of these studies revealed that the expansion population growth model was the best to fit the sequence data. A mean of evolutionary change of 7.84 x 10-3 nucleotide substitutions per site per year (s/s/y) was obtained for the NA gene. A significant contribution of first codon position to this mean rate was observed.

Maximum clade credibility trees revealed a rapid diversification of NA genes in different genetic lineages, all of them containing Oseltamivir-resistant viruses of very recent emergence.

Mapping of naturally occurring amino acid substitutions in the NA protein from 2009 H1N1 IAV circulating in 62 different patients revealed that substitutions are distributed all around the surface of the molecule, leaving the hydrophobic core and the catalytic site essentially untouched.



Conclusions: High evolutionary rates and fast population growth have contributed to the initial transmission dynamics of 2009 H1N1 IAV. Naturally occurring substitutions are preferentially located at the protein surface and do not interfere with the NA active site. Antigenic regions relevant for vaccine development can differ from previous vaccine strains and vary among patients.

http://www.virologyj.com/content/6/1/215

[sharon sanders]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

Oseltamivir resistance is spreading world wide.

Please do not depend on this drug (Tamiflu).

Swine flu - A/H1N1 is not going away. It continues to evolve.

http://www.flutrackers.com/forum/showpost.php?p=326052&postcount=119

[Ronan Kelly]

Tamiflu resistance in A/H1N1 flu - historical compilation of news

Drug resistant H1N1 virus found in Delaware
Wednesday, December 9th, 2009


By: Mark Eichmann
meichmann@whyy.org

While the overall number of H1N1 cases nationwide has been on the decline in recent weeks, health officials are concerned that the virus could mutate to resist anti-viral medication.

The Centers for Disease Control confirmed that a 52-year-old Kent County man who died from complications of H1N1 last month had a strain that showed resistance to antiviral medication. It's the first such case found in Delaware that didn't respond to Tamiflu treatment. State health officials say the victim had a number of underlying health problems that made his fight against H1N1 complicated even without the resistance to antiviral medication.

Director of the Delaware Division of Public Health Dr. Karyl Rattay says the resistance can cause a number of other complications which would require increased treatment efforts. "Someone might be more likely to become dehydrated, so they might need IV fluids. They might be more likely to get a bacterial infection, and if it became widespread, we would certainly expect more deaths."

After examining more than 15-hundred specimens nationwide, the CDC has identified just 15 cases that were resistant to antiviral medication. While the resistant cases represent just one percent of those that were tested, the CDC is asking states to continue sending samples. Their main concern is making sure the drug resistant version of the virus doesn't grow more widespread.

http://whyy.org/cms/news/health-science/2009/12/09/drug-resistant-h1n1-virus-found-in-delaware/25004

[Gert van der Hoek]

Re: Japan - H1N1 - 6-year-old girl is 22nd Tamiflu resistant patient

Seems to be medicine induced

New Flu - Tamiflu resistant - 22nd case from six-years old girl

2009.12.15 17:15

It was announced that the gene mutation that showed the tolerance to the treatment Tamiflu had been confirmed to the virus that gathered new influenza from developing girl (6) as for Mie Prefecture Yokkaichi City on the 15th. Eyes of the example of country 22 according to the Ministry of Health, Labour and Welfare.

It develops on the 16th and it is hospitalized according to the same city though the girl had been taking Tamiflu since October 8 because there was a new influenza infected person in the family.

It left on the 23rd hospital. The gene mutation turned out in the virus inspection afterwards. The infection spread to surroundings is not confirmed.

http://www.excite-webtl.jp/world/english/web/?wb_url=http&#37;3A%2F%2Fsankei.jp.msn.com%2Fregion%2Fkinki%2Fmie%2F091215%2Fmie0912151740002-n1.htm&wb_lp=JAEN&wb_dis=2&wb_submit=+%96%7C+%96%F3+

thanks to Makoto

[sharon sanders]

Tamiflu resistance in A/H1N1 flu - historical compilation of news

via email -


South Korea Reports Death From Tamiflu-Resistant Swine Flu
2009-12-17 06:28:32.171 GMT


By Kyung Bok Cho
Dec. 17 (Bloomberg) -- A South Korean infant died on Dec. 1
from swine flu resistant to Roche Holding AG?s antiviral drug
Tamiflu, the nation?s health ministry said.
The 1-year-old girl, who had brain damage, showed no
response to Tamiflu treatments administered from Nov. 16, even
after the dosage was doubled from Nov. 22, according to an e-
mailed statement today. Tests showed the virus had the H275Y
mutation that makes it resistant to the drug, the ministry said.
It?s the world?s first reported death from a Tamiflu-
resistant strain of swine flu, Yonhap News said.

[sharon sanders]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

"A total of 44 cases of oseltamivir resistant 2009 influenza A (H1N1) viruses have been identified in the United States since April 2009, including 15 newly identified cases since last week."

http://www.cdc.gov/flu/weekly/

[sharon sanders]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

"A total of 44 cases of oseltamivir resistant 2009 influenza A (H1N1) viruses have been identified in the United States since April 2009, including 15 newly identified cases since last week."


http://www.cdc.gov/flu/weekly/

The key word here is "identified". It does not say total.

[Gert van der Hoek]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

"A total of 44 cases of oseltamivir resistant 2009 influenza A (H1N1) viruses have been identified in the United States since April 2009, including 15 newly identified cases since last week."


http://www.cdc.gov/flu/weekly/

This quote seems important too:

Of the 44 total cases identified, 27 patients had documented exposure to oseltamivir through either treatment or chemoprophylaxis, 15 patients are under investigation to determine exposure to oseltamivir, and two patients had no documented oseltamivir exposure.
Occasional development of oseltamivir resistance during treatment or prophylaxis is not unexpected.

So at least 2 patients were resistant without having Tamiflu.

They were infected through other patients in the hospital, or at home? Or wildtype? More details would be appreciated.

[Commonground]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

First Tamiflu-resistant H1N1 case in Utah detected

<!--subtitle-->Rare strain ? Only 29 cases -- excluding Utah man -- have been reported nationally.
<!--byline-->
By Lisa Rosetta
The Salt Lake Tribune

<!--date-->Updated: 12/18/2009 06:20:02 AM MST

Public health officials announced Thursday they have detected the first case of Tamiflu-resistant H1N1 flu in Utah this season.

A Salt Lake County man over the age of 65, with chronic health conditions, was hospitalized earlier this fall with H1N1 and has since been released, said Utah Department of Health spokesman Tom Hudachko.

It wasn't until Thursday morning that the Centers for Disease Control and Prevention (CDC) notified the state that the man's strain is resistant to Tamiflu, a commonly prescribed antiviral drug.

So far the Tamiflu-resistant strain doesn't seem to be circulating in the community, said state epidemiologist Robert Rolfs. Even if it were, those who have been vaccinated for H1N1 flu have protection against it. This particular mutation hasn't changed the virus enough to allow it to resist vaccine-induced antibodies.

Rolfs said getting a high rate of the general population vaccinated is important because it reduces the transmission of the virus and its opportunities to mutate. The health department, however, estimates only 13 percent to 15 percent of Utahns have been innoculated.

"We'd like that number to be closer to 30 or 40 percent to get the type of immunity in the population we'd really need to slow down or prevent a third wave from occurring," Hudachko said.

Tom Skinner, a spokesman for the CDC, said since April there have been only 29 documented cases -- excluding the Utah man -- ofTamiflu-resistant H1N1 in the U.S. Of those, 19 people took Tamiflu to prevent or treat the flu; two did not; and the rest were still being investigated.

The occasional development of resistance to Tamiflu during treatment is not unexpected, he said.

While detecting Tamiflu-resistant strains is important, the CDC would only be concerned if it saw "sustained transmission from person to person going on in multiple places around the country -- that's the kind of clustering we're looking for and we just haven't seen that," Skinner said.

People infected with a Tamiflu-resistant strain can be treated with another antiviral drug, Relenza, though some are too sick to inhale it, he said. Another option is Peramivir, though it has been approved by the Food and Drug Administration only for emergency use. Since the outbreak began, the CDC has received about 1,000 requests to use the drug, which is given intravenously. Its effectiveness is still being studied.

Flu-like activity in Utah has decreased for the seventh consecutive week, but it is still above the statewide epidemic threshold of 1.1 percent of clinic visits, according to the health department's latest report.

There have been a total of 25 H1N1-related deaths this season, including a woman between the ages of 50 and 64 who died last week, the Southwest Utah Health District reported. Hospitalizations due to both H1N1 and the seasonal flu have hit 857, which is 16 more than last week.

The state has now received approximately half of all the H1N1 vaccine it is scheduled to get; as of Dec. 9, an estimated 371,532 doses had been given out. All but two local health departments -- Bear River and Southeast -- are offering the vaccine to the general public.

http://www.flutrackers.com/forum/showthread.php?p=330123#post330123

[estacion]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

According to ECDC Weekly Influenza Newsletter of Dec. 18th, 5 more patients in Netherlands were diagnosed with a mixture of resistant and wild-type A(H1N1)v influenza viruses summing 11 in total to date, of which 4 died

Comments on virological data provided by countries in week 50/2009
The Netherlands
By week 50 in the Netherlands, 11 patients were diagnosed with a mixture of oseltamivir resistant and wild-type A(H1N1)v influenza viruses in one respiratory specimen during oseltamivir therapy, indicating resistance emerged during therapy and not by infection with a resistant virus. Nine of the patients were immunosuppressed due to chemotherapy/immunosuppressive therapy, of which four died. Contact tracing identified no cases of onward transmission of the oseltamivir-resistant viruses.

Source ECDC:

http://ecdc.europa.eu/en/activities/surveillance/EISN/Newsletter/091218_EISN_Weekly_Influenza_Surveillance_Overview.pdf

[Commonground]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

Vietnam

18/12/2009

Vietnam: Save the lives of patients co-infected with H1N1 influenza and SXH [Dengue Hemorrhagic Fever]


Patients was 9 years old girls, Thu Duc district, hemorrhagic fever on the 6th, being treated at a local hospital. Patients do not reduce fever, vascular collapse or be attached hospital moved patients to Children's Hospital 2 ..


Many patients with severe hemorrhagic fever is in the emergency room
Children's Hospital has two tests and positive results for girls influenza A/H1N1. Patients have breathing machine breathing machine NCPAP (continuous positive air through the nose), doctors use tamiflu Nursery 2 days but no results.

Doctors must use more drugs Zanamivir (Relenza) for the patients are stable and then must use a special antibiotic treatment of pneumonia and multiple anti-infection. Results after 2 weeks of treatment, the patient has recovered well and was discharge home.

Dr. Chau Vietnamese warning, in some of today's hospitalized patients with dengue fever reduced the number of cases but admitted the worse. We every day in science only a few dozen dengue patients but six ca weight lying in the emergency departments of science, two patients lying in serious scientific resuscitation in shock due to severe emergency, a new death ca .

http://www.flutrackers.com/forum/showpost.php?p=330043&postcount=7

[sharon sanders]

Re: Japan - H1N1 - man (49) from Nagoya City is 116th death

Japan - #116 death is confirmed to be tamiflu resistant case.


Tami full immunity, the confirmation of four cases in Aichi

2009年12月19日

December 19, 2009

愛知県は１８日、新型インフルエンザに感染して死亡した名古屋市内の男性会社員（４９）から、治療薬のタミ フルが効きにくい新型ウイルスを確認したと発表した。

May 18, Aichi Prefecture, Nagoya-year-old man who died in the pandemic influenza infection (49), the new virus announced it had confirmed the effectiveness of Tamiflu drug resistant.

タミフル耐性ウイルスの確認は全国で２６例目、県内では４例目。

Tamiflu-resistant virus was confirmed in 26 of cases nationwide, in the prefecture of four cases.

死亡した人から確認されたのは初めて。

People were confirmed dead from the first time.

県によると、男性は急性白血病やサイトメガロウイルス肺炎などの持病があった。

According to the County, the man had a chronic disease such as acute leukemia and cytomegalovirus pneumonia.

１０月２５日に発症し、Ａ型陽性を確認。

He developed symptoms on October 25th Sun, A positive-type check.

タミフルやリレンザを処方されたが発熱を繰り返し、１２月１日に新型インフルエンザと診断されて入院したが 、同１５日に急性肺炎で死亡が確認された。

Fever was repeatedly prescribe Tamiflu and Relenza, December 1 had been diagnosed with pandemic influenza hospitalization days, were confirmed killed in the 15 days of acute pneumonia.

http://www.chunichi.co.jp/article/feature/swine/list/200912/CK2009121902000208.html